INHIBITION OF COX-2 EXPRESSION BY LUNASIN-RICH SOYBEAN EXTRACT ON COLORECTAL CANCER
Keywords:Azoxymethane, Colorectal cancer, COX-2, Dextran sodium sulfate, Lunasin
Objective: The incidence of colorectal cancer has been growing faster than most other cancers in the past decade, especially in developing countries. One of the substances that is currently being investigated as potential chemopreventive agent is lunasin, which is contained in soybeans. This research explored the effect of lunasin on COX-2 expression in the distal colons of mice in which colorectal carcinogenesis was induced with azoxymethane (AOM) and dextran sodium sulfate (DSS).
Methods: A total of 30 Swiss Webster mice were separated into six groups. In five of the groups—a negative control group, positive control group, and three intervention groups—carcinogenesis was induced with AOM and DSS; the sixth group received no interventions. Lunasin-rich soybean extracts were given in doses of 250, 300, and 350 mg/kgBW for 6 w to the intervention groups Immunohistochemical staining of COX-2 was then carried out on tissue samples from the distal colons of mice that had been sacrificed. The samples were microscopically assessed and photographed, and cell counts were performed using the Image J application. COX-2 expression is reported in the form of an optical density score (ODS).
Results: Significant differences between the negative control and the intervention groups were found at the 300 mg/kgBW (p = 0.047) and 350 mg/kgBW (p = 0.016) lunasin dosage levels.
Conclusions: This demonstrates that administration of lunasin-rich soy extracts can inhibit COX-2 expression in cryptic epithelial cells of the distal colon in mice with carcinogenesis induced by AOM and DSS.
2. Theodoratou E, Farrington SM, Tenesa A, McNeill G, Cetnarskyj R, Korakakis E, et al. Associations between dietary and lifestyle risk factors and colorectal cancer in the Scottish population. Eur J Cancer Prev 2014;23: 8–17. ?
3. Kristjansson SR, Nesbakken A, Jordhoy MS, Skovlund E, Audisio RA, Johannessen HO, et al. Comprehensive geriatric assessment can predict complications in elderly patients after elective surgery for colorectal cancer: a prospective observational cohort study. Crit Rev Oncol Hematol 2010;76:208–17.
4. Marshall JL. Managing potentially resectable metastatic colon cancer. Gastrointest Cancer Res 2008;2:S23–6.
5. Mishra J, Dromund J, Quazi SH, Karanki SS, Shaw JJ, Chen B, et al. Perspective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol 2013;86:232–50.
6. Anderson JW, Smith BM, Washnock CS. Cardiovascular and renal benefits of dry bean and soybean intake. Am J Clin Nutr 1999;70: 464S–74.
7. Messina M, Flickinger B. Hypothesized anticancer effects of soy: Evidence points to isoflavones as the primary anticarcinogens. Pharm Biol 2002;40:S6–23. ?
8. Liu J, Jia SH, Kirberger M, Chen N. Lunasin as a promising health-beneficial peptide. Eur Rev Med Pharmacol Sci 2014;18:2070–5.
9. Hermandez Ledesma B, Hsieh CC, de Lumen BO. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochem Biophys Res Commun 2009;390:803–8.
10. Hsieh CC, Hermandez Ledesma B, Jeong HJ, Park JH, de Lumen BO. Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable. PLoS One 2010;5:e8890.
11. Wijiasih, Kusmardi, Elya B. The effect of soybean and soybean meal extract on COX-2 and iNOS expression in colon preneoplasia of mice induced by azoxymethane and dextran sodium sulfate. Chem Tech 2017;10:39–46.
12. Dia VP, Wang W, Oh VL, de Lumen BO, de Mejia EG. Isolation, purification and characterisation of lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity. Food Chem 2009;114:108–15.
13. Seber LE, Barnett BW, McConnell EJ, Hume SD, Cai J, Boles K, et al. Scalable purification and characterization of the anticancer lunasin peptide from soybean. PLoS One 2012;7:e35409. ?
14. Kusmardi PB, Harlina E, Cornain S. Inhibition activities of fish oil in iNOS, COX-2, and ?-catenin expressions in colorectal preneoplasia of mice induced by azoxymethane and dextran sodium sulfate. J Appl Biotechnol 2014;2:91-6.
15. Dia VP, Gonzalez de Meija E. Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clustering expression. Cancer Lett 2010;295:44–53.
16. Amalia AW, Kusmardi EB, Arsianti A. Inhibition of carcinogenesis by seed and soybean meal extract in colon of mice: apoptosis and dysplasia. Asian J Pharm Clin Res 2017;10:4.
17. Liu Y, Sun H, Hu M, Zhang Y, Chen S, Tighe S, et al. The role of cyclooxygenase-2 in colorectal carcinogenesis. Clin Colorectal Cancer 2016;16:165–72.
18. Dia VP, Wang W, Oh VL, de Lumen BO, Gonzalez de Meija E. Characterization of lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity. Food Chem 2009;114:108–15.
19. Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 2009;30:183–96.
20. Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S, Mori H. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci 2003;94:965–73.
21. Robertis MD, Massi E, Poeta ML, Carotti S, Morini S, Cecchetelli L, et al. The AOM/DSS murine model for the study of colon carcinogenesis: from pathways to diagnosis and therapy studies. J Carcinog 2011;10:9.
22. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials. Lancet 2011;377:31–41.
23. Wang D, Dubois RN. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 2010;29:781–8.
24. Shao J, Jung C, Liu C, Sheng H. Prostaglandin E2 stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. J Biol Chem 2005;280:26565–72.